17 Hepatitis A

1 143 Hepatitis AHepatitis ADecember 2013 Green Book Chapter 17 v2_017 Hepatitis A NOTIFIABLEThe diseaseHepatitis A is an infection of the liver caused by Hepatitis A virus. The disease is generally mild, but severity tends to increase with age. Asymptomatic disease is common in children. Jaundice may occur in 70 80% of those infected as adults. Fulminant Hepatitis can occur but is rare. The overall case fatality ratio is low but is greater in older patients and those with pre-existing liver disease. There is no chronic carrier state and chronic liver damage does not virus is usually transmitted by the faecal oral route through person-to- person spread or contaminated food or drink. Foodborne outbreaks have been reported following ingestion of certain shellfish (bivalve molluscs such as mussels, oysters and clams that feed by filtering large volumes of sewage-polluted waters) and salad vegetables. Transmission of Hepatitis A has been associated with the use of factor VIII and factor IX concentrates where viral inactivation procedures did not destroy Hepatitis A virus.

2 The incubation period is usually around 28 30 days but may occasionally be as little as 15 or as much as 50 and epidemiology of the disease Improved standards of living and hygiene have led to a marked fall in the incidence of Hepatitis A infection. In the UK, this has resulted in high susceptibility levels in adults, with the typical age of infection shifting from children to older age groups. In 1996, the overall seroprevalence of Hepatitis A in England and Wales was estimated to be 31%, and was 11% among those aged 10 19 years (Morris et al., 2002). Therefore, the majority of adolescents and adults remain susceptible to Hepatitis A infection and will remain so throughout life, with the potential for outbreaks to occur. Hepatitis A infection acquired in the UK may either present as sporadic cases, as community-wide outbreaks resulting from person-to-person transmission or, uncommonly, as point of source outbreaks related to contaminated food.

3 Previously, the incidence of Hepatitis A showed a cyclical pattern in the UK. However, there has been no peak in incidence since 1990 when 7545 cases 144 Hepatitis AHepatitis ADecember 2013 Green Book Chapter 17 v2_0were reported for England and Wales. There were 669 reports in 2004 (HPA, 2005). In Scotland, 26 cases of Hepatitis A infection were reported to Health Protection Scotland (formerly the Scottish Centre for Infection and Environmental Health (SCIEH)) in 2005. This is the lowest annual number of acute cases ever recorded. Acute Hepatitis A infection had been observed to decrease steadily in Scotland from 1993 (241 cases) to 2000 (50 cases).In recent decades in the UK, there has been a number of outbreaks of Hepatitis A among men who have sex with men (MSM). Similarly, outbreaks have also been documented in a number of other European countries. Transmission appears to be by the faecal oral route.

4 Some studies have shown associations with multiple anonymous sexual contacts, particularly in darkrooms or clubs (Reintjes et al., 1999; Bell et al., 2001).Outbreaks of Hepatitis A have also been documented among injecting drug users in several countries. An outbreak among injecting drug users in Aberdeen (Roy et al., 2004) contributed to a major increase in the number of cases in Scotland in 2001 (148 cases). Recently, outbreaks of Hepatitis A in other parts of the UK have involved a high proportion of individuals with a history of injecting and homeless people living together in hostels and shelters (O Donovan et al., 2001; Syed et al., 2003; Perrett et al., 2003). Close contact and poor standards of personal hygiene among these groups, with possible 8000700060005000400030002000100001000800 6004002000 England and WalesScotlandYearTo tal number of reports, ScotlandTotal number of reports, England and Wales19801981198219831984198519861987198 8198919901991199219931994199519961997199 819992000200120022003200420052,5002,0001 ,5001, tal number of cases19801981198219831984198519861987198 8198919901991199219931994199519961997199 819992000200120022003 Figure Number of laboratory-confirmed Hepatitis A reports in England and Wales (1980 2004) and Scotland (1983 2005)145 Hepatitis AHepatitis ADecember 2013 Green Book Chapter 17 v2_0faecal contamination of shared injecting equipment or drugs, appears to be the most likely mode of transmission (Hutin et al.)

5 , 2000; Roy et al., 2004). Hepatitis A is more common in countries outside Northern and Western Europe, North America, Australia and New Zealand. Travel abroad is a common factor in sporadic cases in the UK. The highest risk areas for UK travellers are the Indian subcontinent and the Far East, but the risk extends to Eastern Europe. The Hepatitis A vaccinationThere are two products for immunisation against Hepatitis A. An immunoglobulin provides rapid but temporary immunity. The vaccine confers active immunity but response is not immediate. Vaccines are available as either monovalent, or combined with either typhoid or Hepatitis A monovalent vaccines and those combined with either typhoid or Hepatitis B do not contain thiomersal. The vaccines are inactivated, do not contain live organisms and cannot cause the diseases against which they vaccinesFour monovalent vaccines are currently available, prepared from different strains of the Hepatitis A virus; all are grown in human diploid cells (MRC5).

6 Three (Havrix , Vaqta and Avaxim ) are adsorbed onto an aluminium hydroxide adjuvant. The fourth, Epaxal vaccine, contains formalin-inactivated Hepatitis A particles attached to phospholipid vesicles together with influenza virus haemagglutinin derived from inactivated influenza virus H1N1 (Gluck et al., 1992; Loutan et al., 1994). These vaccines can be used interchangeably (Bryan et al., 2000; Clarke et al., 2001; Beck et al., 2004).Combined Hepatitis A and Hepatitis B vaccineCombined vaccines containing purified inactivated Hepatitis A virus and purified recombinant Hepatitis B surface antigen adsorbed onto aluminium hydroxide (Twinrix ) or aluminium phosphate (Ambirix ), may be used when protection against both Hepatitis A and Hepatitis B infections is required. If rapid protection against Hepatitis A is required for adults, for example following exposure or during outbreaks, then a single dose of monovalent vaccine is recommended.

7 In children under 16 years, a single dose of Ambirix may also be used for rapid protection against Hepatitis A. Both vaccines contain the higher amount of Hepatitis A antigen and will therefore provide Hepatitis A protection more quickly than Twinrix. 146 Hepatitis AHepatitis ADecember 2013 Green Book Chapter 17 v2_0 Combined Hepatitis A and typhoid vaccineCombined vaccines containing purified inactivated Hepatitis A virus adsorbed onto aluminium hydroxide and purified Vi capsular polysaccharide typhoid vaccine (Hepatyrix or ViATIM ) may be used where protection against Hepatitis A and typhoid fever is required (see also Chapter 34 on typhoid).Human normal immunoglobulinHuman normal immunoglobulin (HNIG) is prepared from pooled plasma derived from blood donations. Use of HNIG should be limited to situations where it may have a definite advantage over vaccine. HNIG can provide immediate protection, although antibody levels are lower than those eventually produced by Hepatitis A vaccine.

8 There have been no studies directly comparing the efficacy of HNIG with vaccine for prophylaxis in contacts of cases. HNIG licensed for use for prophylaxis must have a Hepatitis A antibody level of at least 100IU/ml.*Because of a theoretical risk of transmission of vCJD from plasma products, HNIG used in the UK is now prepared from plasma sourced from outside the UK, and supplies are scarce. All donors are screened for HIV, Hepatitis B and C, and all plasma pools are tested for the presence of RNA from these viruses. A solvent detergent inactivation step for envelope viruses is included in the production Vaccines should be stored in the original packaging at +2 C to +8 C and protected from light. All vaccines are sensitive to some extent to heat and cold. Heat speeds up the decline in potency of most vaccines, thus reducing their shelf life. Effectiveness cannot be guaranteed for vaccines unless they have been stored at the correct temperature.

9 Freezing may cause increased reactogenicity and loss of potency for some vaccines. It can also cause hairline cracks in the container, leading to contamination of the should be stored in the original packaging in a refrigerator at +2 C to +8 C. These products are tolerant to higher ambient temperatures for up to one week. They can be distributed in sturdy packaging outside the cold chain, if needed. * HNIG for Hepatitis A prophylaxis is in short supply and, from time to time, alternative products and doses may need to be used. For the latest advice, please check with the Health Protection Agency ( ) or Health Protection Scotland ( ).147 Hepatitis AHepatitis ADecember 2013 Green Book Chapter 17 v2_0 PresentationVaccine Product Pharmaceutical Instructions on handling presentation before use Monovalent Havrix Suspension for Shake well to produce Hepatitis A Monodose injection a slightly opaque, whitevaccines Avaxim suspension Vaqta Vaqta Paediatric Havrix Junior Monodose Epaxal Emulsion for Check for any injection particulate matter Combined Twinrix Adult Suspension Shake the vaccine wellhepatitis A Twinrix for injection to obtain a slightly and B vaccine Paediatric opaque suspension Ambirix Suspension for Shake the vaccine well injection in a to obtain a slightly pre-filled syringe opaque suspensionCombined ViATIM A dual-chamber Shake to ensure Hepatitis A syringe suspension is fully mixed.

10 And typhoid containing a The contents of the vaccine cloudy, white two compartments suspension are mixed as the and a clear, vaccines are injected colourless solution Hepatyrix Slightly opaque Shake the container well white suspension for injection Dosage and schedule The immunisation regimes for Hepatitis A vaccine and for combined Hepatitis A and typhoid vaccine consist of a single dose. The standard schedule for the combined Hepatitis A and Hepatitis B vaccine depends on the product. For Twinrix the schedule consists of three doses, the first on the elected date, the second one month later and the third six months after the first dose. For Ambirix the schedule consists of two doses, the first administered on the elected date and the second between six and twelve months after the first AHepatitis ADecember 2013 Green Book Chapter 17 v2_0An accelerated schedule of Twinrix Adult at 0, 7 and 21 days may be used when early protection against Hepatitis B is required ( for travellers departing within one month).